This is an ongoing, broadly based study of polyamines as biochemical markers of normal and neoplastic growth. Increases in plasma and urine levels of putrescine and spermidine in cancer patients in response to chemotherapy accurately reflect tumor growth fraction and tumor cell loss factor, respectively. These markers are now being used to monitor and design the optimal chemotherapy regime, determine the optimal timing of chemotherapy, as predictors of subsequent relapse to provide a substantial lead time to facilitate timing of adjuvant chemotherapy, to separate the kinetics of regrowth of normal versus malignant bone marrow stem cells, and to model pharmacokinetically polyamines in body fluids. Additionally, we are evaluating whether the levels of polyamines in extracellular fluids are related to the tumor stage and tum r burden utilizing patients with non-Hodgkin's lymphomas in which tumor stage and tumor burden can be accurately established by other means. Because of the importance of a demonstrated spermidine conjugate as a marker of tumor cell kill in response to chemotherapy, we are isolating and characterizing this conjugate and have ongoing plans to develop a radioimmunoassay as so n as the conjugate has been characterized. The importance of ornithine decarboxylase as the possible initiation factor for RNA polymerase I in the control of ribosomal RNA synthesis is further being assessed by purification of the so-far dual ornithine decarboxylase-initiation factor complex to homogeneity, and testing its ability to transcribe new 45S RNA in nucleolar liver preparations in which it is kn wn that only ribosomal DNA genes are active. Substantiation of the dual function of ornithine decarboxylase will be assessed by the ultmate production of antibodies to ornithine decarboxylase. The importance of polyamine biosynthetic enzymes and accumulation patterns in cell cycle progression will be substantiated by inhibition studies in Chinese hamster ovary cells and in HeLa cells.